FDA's final Guidance on Real-World Data and Real World Evidence

Recommendation

12-14 December 2023

Stability by Design - Live Online Training
- Stability Testing in Product Design and Method Development- Focus mainly on small-molecule APIs and drug products

The U.S. Food and Drug Administration (FDA) issued the final guidance on the Use of Real-World Data (RWD) and Real-World Evidence (RWE) to support regulatory decision-making for drugs and biological products.

The guidance is intended to accelerate medical product development and bring innovations faster and more efficiently to the patients. The agency is issuing this guidance as part of FDA's RWE Program to help support approval of a new indication for a drug already approved or to help support post-approval study requirements. In addition, the guidance clarifies the agency's expectations for sponsors using RWD to support the safety or effectiveness of a drug in clinical studies (including interventional and non-interventional designs). According to the guidance,

• an interventional study (i.e., a clinical trial) is a study in which participants, either healthy volunteers or volunteers with the condition or disease being studied, are assigned to one or more interventions, according to a study protocol, to evaluate the effects of those interventions on subsequent health-related outcomes. The potential use of  RWD in interventional studies is, for example, to identify potential participants for a randomized controlled trial (or to ascertain endpoints or outcomes), or to serve as a comparator arm in an externally controlled trial.
• a non-interventional study is a type of study in which patients received the marketed drug of interest during routine medical practice and are not assigned to an intervention according to a protocol (e.g., observational cohort studies, case-control studies).

The document outlines the agency's general expectations for non-interventional (observational) studies. In these studies, various sources of RWD can be analyzed, including registries, electronic health records (EHRs), and medical claims.

Access to RWD and Source Data

The FDA defines RWD and RWE as follows:

• RWD are data relating to patient health status and/or the delivery of health care routinely collected from a variety of sources. 
• RWE is the clinical evidence about the usage and potential benefits or risks of a medical product derived from analysis of RWD.

If certain RWD are owned and controlled by other entities, sponsors should have agreements in place with those entities to ensure that relevant patient-level data can be provided to FDA and that source data necessary to verify the RWD are made available for inspection (including all information in original records and certified copies of original records of clinical findings, observations, or other activities in a clinical investigation used for reconstructing and evaluating the investigation). In addition, sponsors should ensure that RWD and associated programming codes and algorithms submitted to FDA are documented, well-annotated, and complete, which would allow FDA to replicate the study analysis using the same dataset and analytic approach. Moreover, the electronic systems used by the sponsor to manage data and produce required records should comply with 21 CFR part 11 (see also FDA's draft guidance Electronic Systems, Electronic Records, and Electronic Signatures in Clinical Investigations: Questions and Answers).

Sponsor Responsibilities

Sponsors who submit non-interventional studies for regulatory review should take responsibility for all activities related to the design, conduct (including data analysis), and oversight of the studies. These activities should include:

• Selecting qualified researchers to perform study-related activities and confirming that researchers have the skills and information needed to perform their roles in the study
• Ensuring that the study is conducted in accordance with the final protocol and statistical analysis plan (SAP) and documenting any deviations
• Maintaining and retaining adequate study records
• Ensuring that FDA can access and verify relevant records
• Ensuring appropriate study oversight 

The sponsor will retain and make available to the agency upon request a log of any researcher who has significant involvement in the design or conduct of the study (i.e., researcher’s name and affiliations, description of roles or activities performed, qualifications regarding education, training, and experience to perform the proposed study role). If sponsors engage third parties (e.g., data service providers or CROs) to perform certain study-related tasks, sponsors should document the roles and responsibilities of the organization performing the tasks. These documents should be made available to FDA upon request. Sponsors remain responsible for all study-related activities unless a sponsor has transferred its responsibility to a CRO. 

For more information please see FDA's final guidance on Considerations for the Use of Real-World Data and Real-World Evidence To Support Regulatory Decision-Making for Drug and Biological Products.